Quantum Ultimatum 2016 Caterham School

Quantum Ultimatum THE ANNUAL MAGAZINE OF THE MONCRIEFF-JONES SOCIETY

MJ 2015 - 16 ISSUE

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F O R E W O R D

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L A N E

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t the end of last year, I was invited to deliver a lecture to the students and parents of the Moncrieff-Jones Society at Caterham School. I was delighted to share my passion for a scientific explanation of the Origin of Life. Being a researcher in this field I could relay the latest research and data released by my lab. I was so impressed with the enthusiasm the audience at Caterham had for Science, particularly through the excellent questions rivalling those of my university students. I was flattered by the long queue for the book signings after the talk and yet more questions waiting for me.

The tie and notebook presented to me at the end of the talk by the Sixth Form pupils are excellent reminders of such an engaging evening.

Caterham School’s Moncrieff-Jones Society is very special, and is doing great things to develop young people’s love for Science and what it tries to explain. A big thanks to the Head of Science, Mr Quinton, for organising and driving this amazing society over the years, and may I congratulate those Sixth Formers who have given a talk and wish those with talks approaching the best of luck.

May the Moncrieff-Jones Society go from strength to strength in the years to come.

Dr Lane was educated at Imperial College in London, gaining his PhD at the Royal Free Hospital Medical School in 1995 with a thesis researching ischaemia-reperfusion injuries in rabbit autograft. He also became an Honorary Researcher at UCL in 1997 and since October 2013 he has held a position of reader in Evolutionary Biochemistry in the Department of Genetics, Evolution and Environment. He is the author of five books and many articles, winning the 2015 Biochemical Society Award, his most recent being The Vital Question. His overarching theme of research is finding the beginning of life on earth, therefore explaining the title of his lecture, The Origin of Life.

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adies and Gentlemen, I would like to introduce you to this year’s shiny new Quantum Ultimatum.

This annual publication showcases the lectures and talks that have gone on over the past year at the Moncrieff-Jones Society. All are written by the students with no teacher input. With high quality budding scientists comes high quality talks and this year has not broken the trend with some of the best talks I have ever had the pleasure of attending.

For those new to the society and publication, Moncrieff-Jones is a society that runs every fortnight on a Tuesday in which a large number of senior students and teachers pack into the smallest laboratory in the science block and listen to a lecture by one of the Sixth Form on any science topic that they are passionate about. The talks cover a range of topics from the world of theoretical physics to the inner workings of an influenza virus. Each and every talk brings something new to our ears and I can only congratulate those that have undergone the task of presenting.

The talks themselves run in a predictable fashion. Firstly the speakers put themselves in front of an audience to talk for half an hour with nothing but a presentation and their passion for their favoured subject. After the enlightening lecture the student then faces the highly knowledgeable audience in a highly scientific version of Who wants to be a Millionaire? the only catch being there is no money at the end of it, only the satisfaction of answering university level questions. All the speakers put their heart and soul into their talks and researching making it a rewarding experience for them and the students and teachers watching.

Moncrieff-Jones is, in my opinion, the best society that Caterham School has to offer. It focuses on cutting edge science, bringing people together to discuss what they love, and in a society in which science plays such a big part and is advancing all the time, a society which introduces people into this world is invaluable; especially when it is as good as Moncrieff-Jones.

I would like to give a huge thank you to Mr Quinton who has entrusted his society in the hands of Emily and myself, it has been a privilege to be part of it.

The Moncrieff-Jones Society has become a beacon of scientific ingenuity in the school.

Emily and I have had a fantastic time as President and Vice-President and I hope everyone else who has attended has received something from it and can only wish the very best to Hannah and Vlad in the future who take on the task of running the society.

MJ

Treasure this magazine as people have put love and care into what it contains.

Yours Thomas Land

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Contents UPPER SIXTH TALKS

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LOWER SIXTH TALKS

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CLUBS 46

SCIENCE TRIPS

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PAST MONCRIEFF TOPICS

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PAST MONCRIEFF PRESIDENTS, VICE-PRESIDENTS & ENDORSERS

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UPPER SIXTH TALKS String Theory Page 8

Pippa Baliman Philippa is currently studying Maths, Physics and Chemistry. Through a series of highly confusing coincidences, she is going on to study Natural Sciences at Cambridge. She chose her talk on String Theory because it is sufficiently complex and physics based that Mr Quinton wouldn’t be able to notice her constant bluffing.

Antibotics Page 12

Boris Gusev I'm a Russian boarder at Caterham School. I'm currently studying Physics, Chemistry and Biology and will be reading Biochemistry at university. I chose to do antibiotics because I previously did research on penicillin and I wanted to expand my knowledge of antibiotics. Furthermore, antibiotics are very well known for their antibacterial properties, but nothing is taught as to how they are antibacterial, which I thought would be interesting to the MJ society.

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A War against the Influenza Virus Page 14

Eva Wang Hi my name is Eva Wang and am currently in my final year at Caterham school. My two greatest fascinations in life are baking and science, especially that of cell biology and the immune system. I am planning to do Biomedical Science at university. I really enjoyed my Moncrieff-Jones talk because of the interesting questions and all of the positive feedback I had from the audience. It was great fun!

Vision Page 18

Kristina Flexman Hi my name is Kristina Flexman. I find science, particularly Biology and Chemistry mind-boggling, and learning about it at Caterham has given me an amazing perspective of the world. ‘Vision’ is a perfect example of how Biology and Chemistry intertwine to create brilliant systems that many organisms, including humans, reap the benefits of and take for granted on a daily basis without realising the complex beauty behind it.

Black Holes Page 22

Bobby Chan I am currently doing Physics, Chemistry, Economics and double Maths for my A Levels.

I love Physics and the subject that I shall go on to do next year in university. I did my Moncrieff on Black Holes because I wanted people to realise the fun side of Physics and not just the scary equations. The actual detailed physics is hard but after a brief introduction to get it out of the way, it hardly cropped up at all. I can only hope my talk inspired people to learn more about this fascinating subject.

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Pippa Baliman

String Theory One of the fundamental issues with modern physics is the incompatibility between the two greatest theories of our time, quantum mechanics and general relativity. General relativity forms the basis of our understanding of space-time and gravity, whilst quantum mechanics explains the befuddling properties of the microscopic world. Both theories are highly sophisticated and have been shown to work with an extremely high degree of accuracy in their respective environments; when combined, however, the answers generated yield illogical infinities. String theory proposes a solution to this dichotomy.

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In order to understand the conflict better, we must first gain at least a basic comprehension of the two theories in their own right. Within most physical calculations, we must consider an acceleration to be either a change of speed or a change of direction. The effects of acceleration are highly comparable to those experienced within a gravitational field, as seen in the example of the 'sticky wall' ride. The ride involves a spinning cross-section of a cylinder; under acceleration, the rider feels a force pulling the outwards towards the wall, similar to an artificial gravitational field. The effects of acceleration are most visible when analysing the spatial properties of the ride at a standstill and in motion. When the ride is stationary, we could measure its circumference by taking a metre ruler and placing it end to end around the circle; similarly, the radius can be measured by placing the ruler from the centre heading outwards. We find here that, as expected, the circumference shows a proportional relationship to the radius (C=Ď€r 2 ).

However, when the ride is subject to acceleration, this relationship no longer holds, due in part to effects that stem from special relativity. If we assume for this example that the outer edge of the ride is travelling at a very high speed, our ruler held in the direction of motion (along the circumference)

will appear shorter in length to the observer; it is subject to the Lorentz contraction, wherein lengths appear shorter to the outside observer at high speeds. The ruler will appear to fit round the circumference a greater number of times, thereby measuring a greater circumference. As the radial measurement is perpendicular to the direction of motion, the ruler when placed in this direction will no longer be subject to the contraction and will measure the same radius as previously.

The conclusion we can draw from this is that, when experiencing acceleration (or a gravitational field), space (or lengths) and, by extension, time, are distorted or warped. Normal geometrical spatial relationships, such as that between the radius and the circumference, do not hold under acceleration. From this, we can better understand the principle of general relativity, which states that gravity is our experience of the warping of space-time; normal geometry is violated when one tries to take the shortest path between two points, which is not (as seen in fig. 1) a straight line.

QUANTUM MECHANICS This is a much broader theory that encompasses many concepts about how particles interact. It encompasses the Standard Model, a highly successful unification of the three non-gravitational

forces and matter into one theoretical framework. It was the Ancient Greeks who first came up with the idea of a fundamental constituent particle that made up all matter; they termed it the 'atomos', meaning indivisible. Now, of course, we know that things don’t end here. The atom can be subdivided to give a nucleus of protons and neutrons orbited by electrons. According to most A Level syllabi, students are told that these are the fundamental particles making up all matter; this is not the case. Protons and neutrons, it has been discovered, are themselves made of smaller particles known as up and down quarks. With the huge surge in linear and cyclotron accelerators, we have encountered a whole host of other particles, summing to 24 in total (these include 12 antiparticles, the same in properties as their standard partners but exhibiting the opposite electric charge). These particles have been grouped into three families, each containing two quarks, a lepton and a neutrino species. Four force 'particles', commonly termed the force particles, have also been hypothesised. All these particles begin to raise a few questions: why these particles? Why do they possess seemingly random masses and charges? Any change in their properties would cause a massive instability in the universe. String theory sets out to explain why.

The essential concept of string theory is that every point particle is, in fact, a single one-dimensional loop of string, which is the real constituent 'particle'.

The order of magnitude of these strings is around 1020 times smaller than an atomic nucleus, which is why we cannot currently resolve their structures even with our most powerful microscopes.

The strings have a spatial extent but no composition, as they are by definition fundamental. These strings resolve one of the main issues of the Standard Model of particle physics. The collection of particles and their properties are simply values recorded in a table by scientists following experimental observation; we are offered no explanation, no mathematical expression, as to why they possess these properties. From the resonance patterns occurring on strings however, it is possible for us to derive the properties of all the particles. Physicists get quite excited about this.

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Pippa Baliman

Mass is perhaps the easiest of the properties to derive from the waveform of a string. All the strings exhibit vibrations only at discrete resonant frequencies; this is because a whole number of crests and troughs can fit along the string and so the wave will not interfere destructively with itself (nodes remain at 0 amplitude). A relatively large amplitude and a short wavelength are indicative of a high energy wave. We know intuitively that to create a more frantic wave like this, we need to wiggle the string faster (transfer more energy to it). Next, we can relate the energy possessed by the string to the mass of the particle it corresponds to through use of Einstein’s formula E=mc2. What this famous equation tries to demonstrate is the fact that matter and energy are convertible currencies; one can be turned into the other (it is interesting to note that this entails that it is not energy that is constant within the universe but matter-energy). C2 is pretty big as numbers go, which indicates that a small amount of mass will convert to a huge quantity of energy. Therefore, the greater the energy of the string, the greater the mass of the particle it represents.

The other properties of particles can be similarly derived. As the modes of vibration (or waveforms, as seen in the diagram above) are discrete, the properties exhibited by particles must also be discrete and related directly to the progression of harmonics (modes of vibration). This goes some way to explain the discrete values for the particles’ masses.

Having looked at the basis of quantum mechanics, general relativity and string theory, we are now in a position to see how strings set out to resolve the conflict between the two theories. The incompatibility between the two theories stems from the conditions they require. General relativity, which explains how gravity is communicated by the curvature of spacetime, demands a very smooth geometry of space. Quantum mechanics opposes this condition; it states that any region of 'empty' space is in fact highly turbulent on a small scale. It is this disagreement on what happens in the microscopic realm that creates the incompatibility of the two theories.

In quantum mechanics, we are told that, on the smallest level, space is

subject to lots of activity. This arises from Heisenberg’s Uncertainty Principle, which says that if we know with a fairly high accuracy the position of a particle, we will not be able to record its momentum accurately as it will fluctuate dramatically. By defining a region of space, any particles within it will then be able to possess a huge range of energies.

Particles will collide with antiparticles, converting their mass into energy, which will then recondense into particles. High energy or mass within a region will curve space-time and destroy the smooth space of general relativity.

Strings try to solve this problem by calming somewhat the quantum undulations. They do this by 'smearing' the location of particle interactions.

When two point particles (let’s take an electron and a positron) collide, the interaction location is an unambiguous point in space and time, regardless of the velocity or position of the observer, the point has no spatial extent. However, when two one-dimensional strings collide and merge to form a third string, the location is smeared. Different

observers will see the interaction occurring in slightly different places and at slightly different times; no one observer is correct, so we say that the interaction occurs over all these locations. The punch of the force from the two strings colliding is diluted as it occurs over a distance, so calculations begin to yield finite numbers (there are no 'infinite' blasts of energy distorting space-time as dramatically as particles popping in and out of existence). This effect results in a smooth space at subPlanck distances.

String theory continues to intrigue scientists around the world as one of the biggest contenders for a Grand Unified Theory. It manages to incorporate the two greatest scientific theories of the 20th century to yield a very compelling answer to how our universe works.

Should signatures or echoes of these strings be discovered in the macroscopic universe, a monumental paradigm shift would occur. String theory alone has the potential to overthrow our views on the whole universe - and isn’t that what scientific progress is about?

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Boris Gusev

Antibotics The world of antibiotics is a curious one as all of us have heard of antibiotics, we remember that time they have helped us get over an illness and we all know that they kill bacteria. What intrigued me is that besides their antibacterial properties, little of them is taught in A Level syllabi and this lack of knowledge sparked my research into these molecules.

TYPES OF ANTIBIOTICS

Antibiotics are a variety of different molecules which all work in different ways. As such, they have been classified by their mode of action and their effect on bacteria. Contrary to popular belief, not all antibiotics directly kill bacteria.

Those that do are called bactericidal, whilst others that suppress the growth and division of bacteria are known as bacteriostatic.

Furthermore, antibiotics are classified by whether they are broad-spectrum or narrow-spectrum, the former meaning they affect a wide variety of bacteria, the latter describing those antibiotics that only affect a small portion of bacteria or that are specific to a certain type of bacteria.

As different antibiotics have different mechanisms of action, antibiotics are also grouped by how they work.

For instance, all penicillins work by interfering with bacterial cell wall production. Other mechanisms of action include interfering with the function of DNA and affecting protein synthesis.

ß-LACTAM ANTIBIOTICS

β-lactam antibiotics, also known as penicillins, are bactericidal antibiotics.

The common feature of all penicillins is the beta-lactam ring found within the molecules.

The shape of the molecules and the instability of the ring means that the antibiotics rapidly bind to the active site of an enzyme called DD-transpeptidase.

This leads to suicidal inhibition of the enzyme (suicidal because the molecule permanently wedges itself in the active site by reacting with an amino acid residue).

Peptidoglycan (the substance bacterial

Penicillin, the β-lactam ring highlighted in red

cell walls are made of) consists of parallel chains of sugars (sugars being N-acetylglucosamine and N-acetylmuramic acid; NAG and NAM for short) connected together by polypeptide bridges. DD-transpeptidase is responcible for making these protein bridges between the sugar chains.

Inhibiting DD-transpeptidase causes the peptidoglycan cell wall to be weak, which means the osmotic pressure of the cell cannot be withstood, and the bacteria dies by osmotic cell lysis.

Penicillin was one of the first, if not

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the first, antibiotics to be discovered, and as such bacteria have developed resistances to β-lactam antibiotics.

There are a couple ways the bacteria have aquired resistance. One such way is the mutation in the gene coding for DD-transpeptidase, changing the shape in such a way that it can still form polypeptide bridges needed to hold peptidoglycan together, but reducing the afinity of penicillins to the enzyme. Another way is the creation of penicilinase, an enzyme that breaks down the beta lactam ring of the antibiotics, rendering it useless.

Resistance to this antibiotic comes about from mutations in the genes' coding for the two enzymes', which alter the enzymes shape to reduce their binding affinities with fluoroquinolones. It is important to note that for resistance to be acquired, both enzymes need to be changed.

Sulphonamide functional group

of folate. Sulphonamides compete for the active site of DHPS with 4-aminobenzoic acid (also known as PABA). The reason for the inhibition is obvious when looking at the structure of an example sulphonamide and PABA. Their similar structure (highlighted in red) explains the cause of competitive inhibition.

Resistance to sulphonamides comes in a couple of ways. As these antibiotics are competitive inhibitors, simply increasing the concentration of PABA will overcome the negative effects of the antibiotic. Furtermore, efflux pumps have also been observed, which pump the antibiotic outside the cell (this is not exclusive to this antibiotic). Lastly, some bacteria have also evolved a different pathway for folate synthesis, bypassing DHPS step completely.

Sulphonamide antibiotics are molecules with the sulphonamide functional group.

The sulphonamide functional group in itself does not exhibit antibacterial properties, the antibiotics were just named after the functional group, which they contain.

Sulphonamides inhibit vitamin B (also known as folic acid or folate) synthesis. As folic acid is used in maintanence of the cell and DNA and RNA synthesis, inhibitng its production halts cell growth and division, hence the bacteriostatic effects of sulphonamides.

Sulphonamides don’t affect mammals as they obtain vitamin B from diet, rather than synthesising it themselves.

Sulphonamides competititvely inhibit an enzyme called dihydropteroate synthetase (DHPS for short), which is one of the enzymes used in the synthesis

As I’m sure many of you are aware, there is a big problem of bacterial resistance around the world, with strains of bacteria like MRSA making the news. Many antibiotics are already losing effectiveness against bacteria as they evolve resistance mechanisms.

This is a big problem as antibiotics are extensively used for treatment of diseases and infections.

One way to solve the problem is to develop new antibiotics, which is easier said than done. However recently a new technique for growing bacteria in laboratories was developed, which allows for bacteria that previously would not grow in vitro to be cultivated. This means that a whole new population of bacteria is open for research, with some of them potentially having never seen antibiotics.

SULPHONAMIDES

FLUOROQUINOLONES

Fluoroquinolones are broad-spectrum antibiotics which work by interfering with DNA replication. Their target enzymes are topoisomerase II and IV, the former also know as DNA gyrase.

Topoisomerase II removes supercoiling of DNA that happens due to the replication fork moving forwards.

For DNA replication to continue, this supercoiling needs to be removed.

Fluoroquinolones bind to the DNAenzyme complex, making it more stable.

This in turn inhibits the enzymes function and can cause breaks in DNA. Multiple breaks in DNA can kill the bacteria.

Topoisomerase IV is responsible for unlinking the two bacterial DNA loops that are produced after DNA is fully replicated. To do this, DNA has to be broken and reconnected. By binding to topoisomerase IV, fluoroquinolones again inhibit it from doing its function, which will leave DNA cut without being reconnected. This is also fatal for bacteria.

The general molecular structure of Fluoroquinolones. The fluorine atom in red is what gives the ‘fluoro’ in the name. The fluorine atom increases the binding affinity to target enzymes.

PROBLEM OF RESISTANCE

PABA (left) and Sulfamethoxazole (right). Aminobenzene highlighted in red.

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Eva Wang

A War against the Influenza Virus Influenza, commonly known as 'the flu', is an infectious disease of the respiratory tract caused by the influenza viruses. It was responsible for the 1918 Spanish Flu and claimed an estimated 50 to 100 million lives.

Still today seasonal influenza is responsible for thousands of lives each year in the UK.

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STRUCTURE The influenza viruses are RNA viruses that belong to the family of Orthomyxoviridae. Roughly spherical, Influenza A virus contains a genome of eight single-stranded RNA segments, enzymes required for viral replication inside a host cell, and a shell of matrix proteins. The virus also has a phospholipid envelope with several embedded proteins, including haemagglutinin (HA) and neuraminidase (NA) – which are used in the naming system of different strains of influenza viruses. Currently, eighteen types of HA protein (H1-H18) and eleven types of NA protein (N1-N11) are known, giving many potential combinations.

LIFE CYCLE Influenza is normally transmitted by droplets or aerosols from the sneeze or cough of a nearby, infected person.

In humans, the primary targets for influenza viruses are epithelial cells in the upper and lower respiratory tract. A potential host cell has receptor proteins on its plasma membrane that contain poly-saccharides terminating with sialic acid. This provides a recognition site to which the virus’ haemagglutinin protein binds, causing receptor-mediated endocytosis to occur and the virus enters the host cell in an endosome.

As the endosome matures, the pH drops. As soon as the pH within the endosome drops to about 6.0, the original folded structure of the HA molecule becomes unstable, causing it to partially

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unfold and release a hydrophobic fusion peptide chain that was previously hidden within the protein.

The fusion peptide inserts itself into the endosomal membrane and acts as a molecular grappling hook that locks on. As the rest of the HA molecule refolds into a new structure (one that is more stable in acidic condition), it 'retracts the grappling hook' and pulls the endosomal membrane right up to the viral membrane, causing the two to fuse together. Once this has happened, the viral genome and associated proteins (viral Ribonucleoprotein complexes – vRNPs) are free to be released into the cytoplasm.

The release of the vRNPs into the cytoplasm is also facilitated by acidification of the viral interior prior to the endosomal-viral fusion step.

This opens up the M2 ion channels on the viral envelope, which is a protonselective ion channel that allows influenzaprotons (H+) to flow into the viral interior, weakening the interaction of the M1 (matrix) protein layer with the viral envelope and the vRNPs. Influenza viral transcription occurs in the host cell nucleus, therefore after being released into the cytoplasm, the vRNPs must enter the nucleus. This is facilitated by the nuclear localization signals carried by the incoming vRNPs. The influenza virus has a negativesense (3’ to 5’) RNA genome, and so unlike positive-sense RNA, cannot be directly translated into protein. In the nucleus, the negative-sense viral RNAs are first transcribed into positivesense mRNAs by the RNA-dependent RNA polymerase, which is part of the incoming vRNP complex.

The negative-sense viral RNAs also serve as templates for production of exact positive-sense RNA copies, which in turn direct the synthesis of many new copies of the original negative-sense viral RNAs. These genomic segments are transported back into the cell cytoplasm for assembly of new virus particles.

Synthesis of the viral envelope

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proteins HA, NA and M2 takes place in the cytoplasm. Afterwards, the proteins are transported through the Golgi body and the trans-Golgi network to the plasma membrane of the host cell. There all the viral components assemble and begin the budding process.

After budding, the new virus particles are still attached to the cell surface membrane through interaction of the HA with sialic acid residues on receptor proteins. This is where NA plays an essential role in the exit of the newly synthesised virus particles. The viral NA cleaves the sialic acid, and so releases the viruses from the host cell’s surface, allowing them to spread further throughout the respiratory tract.

PATHOGENESIS The influenza virus is notoriously known for its ability to cause recurrent epidemics and sometimes global pandemics, during which acute respiratory distress syndrome occurs explosively in all age groups.

The entire process of viral infection seriously disrupts the normal physiology of the cells. However, in fact, most of the time what is horrible about influenza is not the virus particle itself, but the related complications it leads to. Those who are infected are often prone to secondary bacterial infection, with special mention to bacterial pneumonia which causes serious morbidity and mortality. Another way an influenza infection can induce death is through the action of a cytokine storm. This is when an immune response is so powerful that it actually damages the body.

hand, M2 protein inhibitors work by preventing the virus from taking over the host cell and so interfere with the replication process.

PREVENTION Whilst treatment is available for influenza infections, some virus strains have already developed resistance to these antiviral drugs. For example, measured resistance to M2 protein inhibitors in American isolates of H3N2 has increased to 91% in 2015. Ideally, we should focus more on preventing influenza epidemics rather than having to deal with the aftermath.

Of course, keeping good hygienic habits plays an important role in reducing the transmission of influenza. However, equally essential is the provision of immunisation from seasonal influenza vaccine. This protects against the influenza viruses that research predicts will be the most common during the upcoming season. Vaccination may be administered as an injection or as a nasal spray.

DIFFICULTIES It is not practical to predict with certainty which flu viruses will predominate during the upcoming season because firstly influenza viruses are changing all the time via antigenic drift and shift;

secondly, experts must pick which viruses to include in the vaccine many months in advance in order for vaccine to be produced and delivered on time.

Therefore it is perfectly reasonable for there to be a mismatch between the circulating viruses and the viruses in the vaccine.

A UNIVERSAL VACCINE? Research has been carried out on a universal influenza vaccine, which ideally will be able to combat different strains of viruses within Influenza A. It works by targeting the part of the influenza virus that remains relatively stable and unchanged from year to year. An example of this is the ‘stem’ of the HA protein.

However, in my opinion the public should not be so optimistic about this scientific breakthrough. This is because even tested safe, no one can guarantee that it will remain effective in the long term. The sudden boost in selection pressure may prompt the genes coding for the HA stem to mutate just as frequently as the ones coding for surface head proteins. Antigenic drift may again become an annoying problem in the manufacture of a perfectly matching vaccine. Perhaps sadly, our war against the influenza virus is indeed predestined to be never-ending.

TREATMENT There are two classes of antiviral drugs used against influenza: neuraminidase inhibitors and M2 protein inhibitors.

Treatment with antiviral drugs can reduce the duration of symptoms and the time to recovery by one to two days.

Neuraminidase inhibitors can block viral NA activity because they are structural mimics (competitive inhibitors) of the sialic acid residues, to which NA binds to release the virus particles from the infected cell. As a consequence virus infection is inhibited because the virus particles cannot spread from one cell to another. On the other 17

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Kristina Flexman

Vision

It amazes me how, through the medium of molecules humans can percieve the world around us and generate chemical maps in our brains of our surroundings. This extravagant biochemical pathway is probably taken for granted by most of us, even though it is something most of us rely on every day. We know for a fact that we can see but the question is, what actually is seeing?

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T

he action begins inside the rods and cones, which are the photosensitive cells of the retina that actually absorb light. The rods and cones do this in a similar way, except cone cells are more fascinating because they allow us to interpret colours.

What is really incredible about cone cells is that humans only have three different types of cone cells, one type for short wavelength (blue light), one for medium wavelength (green light), and one for long wavelengths (red light). Yet, with these three types, humans can distinguish between about 10 million different shades of colours. This is because there are about 6 million cone cells in your retina, and it is the extent to which each of the 6 million cone cells is stimulated that actually creates different colours in our minds.

This phenomenon is known as trichromacy and, yes, it is impressive that we can see so many colours with just three types of cone cells. However, there are many organisms with much more elaborate visual systems than us. Some animals, including pigeons, have pentachromacy which means they can see about 1000 times the number of colours as us. That is the same as trying to come up with 1000 new colours for the spectrum.

At a molecular level the process in our eyes all starts with a molecule known as retinal (structures shown by figure 2) which is covalently bonded to a protein known as an opsin (the different types of opsins allow for different types of photoreceptor cells, as they have different permeabilities to different light wavelengths).

The opsins are embedded in the membrane of a cone cell or a rod cell.

Retinal is the actual photon absorber in our eyes. Retinal is special because the carbon carbon double bonds shows cis-trans isomerism. Due to carbon to carbon double bonds restricting rotation, the groups of atoms bonded to the carbons in the bond can be arranged in

Figure 1 – The three dierent types of cone cells and their absorption peaks

different orientations, allowing for different isomers. The isomers of retinal that exist naturally in our eyes are 11-cis-retinal (figure 3) and all-trans-retinal.

Before any light absorption happens, retinal is in the form of the 11-cis retinal. If a photon hits the electrons in the 11-cis double bond, it can excite them, and promote them from the bonding orbital into an antibonding orbital. This means that the double bond is temporarily broken, allowing free-rotation around the bond, which is now acting as a single bond. Before the excited electrons fall back down into their bonding orbital, the hydrocarbon chains either side of the bond rotate, causing isomerism of 11-cis-retinal into all-trans-retinal, in order to achieve a lower internal energy of the molecule.

Now the significance of this isomerism is that the retinal is bonded to opsin so, as the molecule changes shape, the retinal no longer actually fits in the binding site of the opsin, so the complex splits, releasing the all-trans retinal, which is recycled in the visual cycle where it is converted back into 11-cis-retinal. After the

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hv

splitting, the binding site of the opsin is exposed enabling it to bond to a multi-subunit protein called Transducin.

The bonding of Transducin to the opsin causes an immediate change in the tertiary structure of Transducin, making it dissociate from GDP (Guanine Diphosphate), which it is bound to when inactive, and in place of GDP it binds to a cofactor: GTP (Guanine Triphosphate). This molecular swap triggers the alpha subunit of Transducin to detach from the other subunits, freeing the alpha subunit to bond to and activate a type of enzyme known as a phosphodiesterase.

The role of this phosphodiesterase is to prevent the entry of sodium ions (Na+) into the cell. It does this by breaking down cGMP (Cyclic Guanine Monophosphate - a molecule found in the cytoplasm of the cell), into GMP, hence lowering the concentration of cGMP inside the cell. This works because the Na+ channels in the cone cell membrane are only open when bound to cGMP, so if there isn’t enough cGMP present, they close, preventing entry of sodium, causing hyperpolarisation of the cone cell.

Then, this hyperpolarisation causes voltage-gated Calcium ion (Ca2+) channels to close, so the Ca2+ concentration in the cone decreases, which directly inhibits the release of neurotransmitter by the cone cell, because fusion of the neurotransmitter vesicles

Figure 2 – photoisomerism of the 11-cis isomer of retinal into all-trans retinal.

(Systematic name for retinal: 3,7-Dimethyl-9(2,6,6-trimethylcyclohexen-1-yl)nona-2,4,6,8tetraenal)

to the cone cell membrane requires Ca2+, so less neurotransmitter reaches the next part of the retina. This highlights another interesting thing about cone cells; usually receptor cells release neurotransmitter in the presence of a stimulus, but cone cells do the inverse - they release neurotransmitter in the absence of light and in the presence of light they stop.

Finally, the cascade is deactivated by an enzyme called GC (Guanylate Cyclase), which hydrolyses the GTP, found in the transducin alpha subunit, into GDP, so the subunit breaks off from phosphodiesterase, deactivating it, so the Na+ channels reopen. Also, it converts GTP to cyclic GMP, allowing the Ca2+ channels to reopen, so neurotransmitter is once again released.

Then the message is conveyed to the visual cortex in the brain via a series of neurones and specialised cells.

So now you know that sight is merely our brains manipulating different quantities of neurotransmitter from our optic nerves in order to generate 'images' of our surroundings - but what we perceive as images are really just thousands of chemical interactions in our eyes and brains. Without opsins there would be no red, green or blue, and without tiny little retinal we would not have our incredible sense of sight. To me, the biochemistry behind vision really captures the power of chemical reactions and evolution.

Figure 3 summarises the events in cone cells: Step 1: light is absorbed by retinal in opsin. Step 2: the opsin bonds to transducin, which releases GDP and binds to GTP. Step 3: the alpha subunit of transducin dissociates, and bonds to phosphodiesterase. Step 4: phosphodiesterase breaks down cyclic GMP into GMP. Step 5: Na+ and Ca2+ channels close.

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Black Holes Bobby Chan

To understand black holes, we first need to understand gravity because it is the core of a black hole's behaviours and properties.

Although we still can't properly explain gravity, we have a fairly close model to understand gravity - Einstein's Theory of Relativity.

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SPACETIME

Now we need to put our common sense aside because it will get in our way of understanding the theory. So to begin with, the first thing we need to know is spacetime. Spacetime is a concept emphasised in the theory of General Relativity (GR), it essentially suggested the combination of space and time. So forget about your common sense, we now have to accept that space and time are not two separate things and they are even similar in a sense. Time is just another dimension that we travel along, like space, and we can therefore put coordinates to indicate an event, like how we do with a location in space. So instead of locating you by three spatial coordinate (one coordinating system for example: longitude, latitude, and sea level), we can locate the event of you reading this essay in spacetime : time (when are you reading it), and the three spatial coordinates. We can, therefore, try to visualise spacetime by the 'loaf of bread' analogy : We cannot visualise a 4D image because out brain is not used to it but we can 'cut' off one dimension and picture it as a loaf of bread where each slice is purely spatial and time flows as we go along different slices.

WARPED SPACETIME

Any dimension, like a 2D plane on a paper, dimensions can be 'bent' (warped) in a sense. An ant walking on the paper would not notice that the paper is bent, we as living beings that perceive three space dimensions + one dimension, would not realise that our dimensions are also warped. We also need to know that mass can warp spacetime; we cannot ask why or otherwise this will go on forever and this is as deep as we need to go now.

Keep this thought in mind because we will need it later on.

GEODESICS

Geodesic is just a fancy term meaning the shortest distance between two points.

It is simple when we are looking at a piece of flat paper because it is just the straight line between the points. But the geodesics in a curved surface are not necessary a straight line, for example the shortest distance between two point on the surface of a sphere is not the straight line across, but the great circle which passes both points. With this being said, we can almost be certain that the geodesics in the warped spacetime are not just straight lines.

UNDERSTANDING GRAVITY

To make it simple, we can assume two rule that most matters follows, i. Matter only follows its geodesic in spacetime without an external interference ii.Matter has to travel through sapcetime - so it either travels (at the speed of light) through space or time, or both, but cannot stay stationary in spacetime.

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This is the time to forget about the high school Science textbook, gravity is not a force, it is instead a consequence of the above two rules.

It might seem weird because this is completely different from what we have been told growing up but let's imagine the following example:

Again we have 'cut off one dimension'.

Imagine our spacetime as the flat sheet, it is now warped so that it is no longer flat, and it is 'curving down like a dimple'.

Now remember that mass can warp spacetime, just like the dimple (imagine a small rock on a flat trampoline). In this way, because we know that matter will follow its geodesics and it has to travel through sapcetime, they travel 'into' the dimple without noticing its curvature (following the arrows). This means that matter will appear to go towards masses, giving the phenomenon we known as gravity.

GRAVITATIONAL TIME DILATION

If both you and I walk towards the North Pole following the shortest path (the great circle) and we are also starting with a parallel path, once we have reached the North Pole however, we meet and we would both agree that we have definitely travelled on the shortest straight line (our geodesic) in parallel. We therefore suggested that there has to be a force pulling me and you towards each other during our journey and in a similar way to this analogy, people named this gravity.

Now instead of a sphere, lets imagine our warped spacetime

Now after we have very briefly introduced the concept of spacetime, we can start to explore a black hole's properties. If you have watched the movie Interstellar, you will know that time travels slower near a black hole.

With what we have discussed in this essay, we can have a very simplified explanation of that. In fact, not just black holes but time flows slower near any masses, even me and you (it's just that the time slows by such a tiny amount that we do not notice). By skipping the most important calculations and algebra, the simplest reason would be the fact that we cannot see the warping of spacetime around us.

We can only see the red line as a distance travelled through spacetime because we cannot realise that actual warping takes place (represented by the blue line), so if we fired a light beam from left to right, it would take a 'longer path' than what we would have expected, so the light beam would take a longer time to reach us.

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Because we know that the speed of light is always constant, the time must have travelled slower.

ESCAPING FROM A BLACK HOLE?

The introduction of spacetime also gives us a very good way to imagine a black hole's 'trapping power'. The reason why you cannot escape from a black hole can be explained by the extreme warping of spacetime inside a black hole. The time dimension is so warped that it is going as if towards the black hole itself, this means travelling through time is almost like travelling in space. If we wish to go to the future, we would go close towards the centre of the black hole.

This also implies that to escape from a black hole, we will need to go back in time, which would pretty much be impossible because it will break all laws of physics.

FORMATION

To make it easier to explain, I will use a very poor description where gravity pulls you. So the reason why we are not pulled by the gravity straight into the centre of the Earth is that the earth underneath is strong enough to withstand the pull, so our Earth will not collapse. And for a star, it is due to the continuous nuclear fusions which created a large outward pressure to balance the inward gravitational pull.

But once a star runs out of fuel, it can no longer provide the outward pressure and it will collapse due to the enormous gravitational pull from the centre of the star.

If the star is so massive that there is nothing strong enough to stop this implosion, the star will collapse to a single point known as a sigularity and a black hole will form. There are also other ways to form a black hole, but the most common way is this kind of star implosion.

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Bobby Chan

GRAVITATIONAL LENSING

This is the very interesting phenomenon of a black hole and its surroundings.

Because the gravity effect is so strong near the black hole, even light gets bent so what is behind the black hole would be seen around the black hole because the light coming from the object behind it will bend around the black hole.

And the accretion disc (which is mostly

rock and dust that is forced to orbit around the black hole due to gravity) will appear like this because the light coming from the back of the disc bends around the black hole so that it appears to be on the top/bottom.

SINGULARITY

A singularity is not just the point where all the mass of a black hole is concentrated, it is defined as the location in spacetime where the warping is infinte.

So of course that point is a singularity, but there are also other types of singularity. The point where all the mass locates is similar to the type called BKL Singularity. It is very violent, atoms and molecules are distorted so much beyond recognition. On the other hand, there are some gentle sigularities such as the mass inflation singularity. It forms behind the infalling observer as all the matter and energy falling into the black hole after the observer, piles together and forms a

singularity. This is so gentle that there is a possibility of surviving even when we have reached this singularity. With the same argument, there would also be a singularity created by everything that falls into the black hole before the observer falls in. The material (photons, gas, gravitons, etc) that falls into the black hole is at some point reflected back out so there is an outgoing stream.

This is called the shock singularity. But after all, all laws of physics do not work at singularities, so no one really knows what's going to happen when we reach it.

Quantum Gravity, or more Overall, black holes have been a great mystery of Physics in our time, and it has opened up a lot of questions for physicists. It is pushing for a new breakthrough in Physics where we will need more than our current theories to understand our universe.

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LOWER SIXTH TALKS Human Augmentation Page 28

Matthew Hogan My name is Matthew Hogan and I decided to do my Moncrieff on Human Augmentation. I chose this topic because of the interesting (and multidisciplinary) science behind it, spanning from nervous biology to complex physics. Its wide range of applications including rebuilding lives and the enhancement of all humanity; means this technology will change the very fabric of society.

The Genetics of Breast Cancer Page 32

Hannah Pook My Moncrieff-Jones talk was entitled ‘The Genetics of Breast Cancer’, a topic which has always fascinated me as a medic. I wanted to know more about the different genes that increase the risk of developing cancer, especially considering the large number of people who suffer from it today. I hope you enjoy reading my article as much as I enjoyed researching and writing it.

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Hearing Page 36

Vlad Kalinovsky Hello! My name is Vladimir Kalinovsky and currently I am studying all three sciences and double maths as my A Levels. I chose Hearing as my MJS talk topic because there is a large number of people who don’t actually know how they hear, not surprising considering it is one of the most complex and delicate structures in the entire body. I can only hope people took vital knowledge away from the talk as they learnt about themselves and one of the most important systems in the body.

Pigmentation of Dinosaurs Page 40

Alice Fish I currently take Biology, Chemistry, French and Theatre Studies. When I was ten I wanted to become a forensic scientist, today however I’m more interested in the deceased, they have just been dead a little bit longer (also, who doesn’t love dinosaurs?). We see many pictures of these ancient reptiles, some with feathers, some green, some red and ever since I was little I wondered how we knew what colours these creatures could have been. As it turns out, we didn’t, until recently.

Parkinson’s Page 42

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Raymond Ho Nothing gives you more satisfaction than doing a successful Moncrieff Jones talk with lots of fun and interesting questions afterwards. At least that was what I first thought. Oh, wait. Where are my manners? I forgot to introduce myself! My name is Raymond Ho, and I do Triple Science and Double Maths. I am a big fan of science, of which I especially marvel at the design of the brain; at how such a small structure can grant us all the imagination, logic and colours of the world. After doing my Moncrieff, I found out there is strong scientific evidence that suggests “Nothing will give you more satisfaction than doing another Moncrieff Jones!”

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Human Augmentation Matthew Hogan 28

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t is in human nature to restore what is lost and enhance what is there. This is particularly prevalent in the fields of prosthetics and augmentation, where the most basic restoration of function to the most cutting edge implants can be seen.

From an engineering perspective, it is easy to make a prosthetic look like an arm, leg or eye, but an entirely different matter to make it act like one. Aesthetic prosthetics have been around since the Egyptians, with replacement toes for wealthier members of society, and the most basic restoration of function, in the form of peglegs for pirates from the 1700s. However, for full restoration of severed limbs, there is still a long way to go.

Current technology is progressing faster than ever before, in the fields of ergonomics, mimetic (i.e. how the limb looks), materials and interfacing. This

has led to the development of prototypes of prosthetic hands which can feed back temperature stimuli to the brain and others with a tactile sense, to (partially) restore the feeling of touch and pressure. Advances in manufacturing technology have led to drastic reductions on cost.

Over the years there have been advancements in artificial limbs. New plastics and other materials, such as carbon fibre, have allowed artificial limbs to be stronger and lighter, limiting the amount of extra energy necessary to operate the limb. This is especially important for above the knee amputees.

Additional materials have allowed artificial limbs to look much more realistic.

Interfacing Interfacing is how and where the artificial limb meets the body and is controlled by it. This is the area in which the most drastic advances are made, such as those to do with thought control and sensory feedback.

Typically a modern day prosthetic limb is attached via the stump and socket method, this method has been around since prosthetics were invented, and is the simplest and cheapest method to utilize, however it can have significant drawbacks compared to direct bone integration, or osseointegration. The stump and socket method can cause significant pain to the amputee, and this is why osseointegration has been explored. Osseointegration can be utilized by inserting a titanium bolt into the bone at the end of the stump, and over the course of a couple of months the bone attaches itself to the bolt. Then,

is osseointegration, by definition 'the formation of a direct interface between an implant and bone, without intervening soft tissue'. The main reason this can happen is due to titanium’s high biocompatibility.

This phenomenon was first observed on 1940 by the researchers Bothe, Beaton and Davenport. They realised titanium’s ability to fuse with bone, together with its hardness, would make it a good prosthesis material. Eleven years later, it was described by Gottlieb Leventhal, who, after placing titanium screws into rat femurs, noted how 'At the end of 6 weeks, the screws were slightly tighter than when originally put in. At 12 weeks, the screws were more difficult to remove and at the end of 16 weeks, the screws were so tight that in one specimen the femur was fractured when an attempt was made to remove them'.

Titanium is highly biocompatible, allowing it to bond to the bone where other metals cannot. It is considered to be the most biocompatible of all metals due to its bio-inertness, capacity for osseointegration, and high fatigue limit. This ability to withstand the harsh bodily environment is a result of a protective oxide film that forms naturally on titanium in the

a rod (called an abutment) is attached to the bolt, extending it through the skin. The prosthesis is attached to this protrusion. This allows for better muscle control of the limb, as well as the ability to wear the prosthetic for extended periods of time. However, this method has a significant drawback, as the limb cannot be subject to large, sudden impacts, such as those experienced in jogging and running, because it can cause the bone to crack and, in extreme cases, fracture.

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presence of oxygen. The oxide film is strongly adhered, insoluble, and chemically impermeable, preventing reactions between the metal and the surrounding tissue.

The strength of the bonding also depends upon the oxide layer. The thin layer reacts, very slowly, to extracellular fluid - bonding with phosphate and hydroxyl groups. This bonding polarises the oxide layer, which in turn polarises the titanium in a positive feedback loop (due to the dielectric effect, where particles line up with an electric field). The diverse nature of the titanium surface leads to absorption and bonding of lipoproteins and glycolipids, initiated by the polarized nature of the surface. This ‘mess’ of large molecules now covering the surface of the titanium is quite porous and leads to more molecules bonding. Usually, the tissue surrounding an implant would become inflamed, leading to reduced function of the limb; however, the biological molecules bound to the surface prevent this. It also protects the titanium from corrosion; extending the life on the implant dramatically (some titanium cleft implants have been installed for over 50 years without needing replacement).

Moreover, in the short term, the biological molecules that are normally found on the implant’s surface mask its presence from the immune system, reducing the risk of an immune response and rejection. Over time osteoblasts (bone secreting cells) settle in the area, and bone grows around the implant. The implant does not grow on you, you grow on it.

Control Now that our arm is integrated into the body, the question is now one of controlling it. This can be done in a variety of ways, ranging form switches that the user presses on the shoulder to directly interfacing with the motor cortex of the brain. The two main ones I will focus on are Myoelectric Interfaces and Electrode Interfaces. There are two main differences between the two, the invasiveness of the implant and the sensitivity.

A similar factor used in both of these control methods is that the hardware to control the limb is still present in the amputated body i.e. all the nerves and

part of the brain required to control the limb are still present. Therefore, the amputee can still think about moving the amputated limb and the relevant nerves will fire; however, these impulses are sent to the severed nerve endings and so are terminated. This means that if you were to receive these signals you could use them to control an artificial limb. I write this as if it were theory; however it has actually been done by Dr Kevin Warwick, who implanted a neural interface into the median nerve (on the back of the forearm) of his own arm. The interface contained 100 electrodes and could be used to pick up signals from different nerve bundles.

The signal detected was more than clear enough to control a robotic hand, which

a colleague of his, Dr Kyberd, went on to build. Through a system of trial and error they successfully mapped electrode pins in the array to actuators in the hand, enabling natural movement of the robot. This experiment was taken a step further when the implant was connected to the internet in New York, to allow for remote control for a robotic arm situated in Reading University. Quite the feat of engineering. In addition to this, the electrode works both ways.

Dr Warwick could also 'feel' (receive sensory information about) objects the hand was holding in England while in New York himself.

The above experiment was an example of Direct Nerve Interfaces.

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These are useful and can provide a more accurate signal than a non-invasive sensor (since they are attached directly to the neurones); however, complication can arise, as the electrode is stiff and does not deform in the same way tissue does.

This can lead to tissue shear, causing inflammation and scar tissue to grow over the site, impeding the signal being picked up from the electrode. This is a serious problem for long term implants; however, these problems do not always manifest themselves.

There is a way to avoid these problems in there entirety; by using Myoelectric Interfaces with nerve rerouting. These interfaces get around the problem of nerve inflammation by not

actually being in the body. They instead rest on the skin, which predictably makes the signal harder to detect since it is weaker. Whilst this is the main disadvantage, another is lack of fidelity, unless nerve re-routing surgery is performed. The component that detects the changing membrane potential as it moves along the nerve is called an electromyography.

This rapid change of charge along the surface of the plasma membrane is a nerve impulse and both the direct neural interfaces can detect them; however, the fidelity required for fine motor control is impossible with the current myographical technology. In addition to this, even though Myoelectric controllers provide

incredible control over an artificial arm, patients have been known to prefer to use simpler, mechanical prosthetics. For one thing, such devices allow the patient to sense the movement of the arm through a system of cables, which are used to control the device, usually by attaching them to the opposite shoulder. Therefore, even when their eyes are closed they can get a sense of whether an artificial arm is extended or if there is resistance to a grasping motion, making the limb feel less detached and unnatural than an EMG device. Another problem with EMG prosthetics is that patients have to retrain their brains to make new associations between muscle movements and their outcomes—a shoulder flex could become a grasp motion, for example, while a twitch of pectoral muscle in the chest may extend the artificial arm.

However, there is a way to overcome both these difficulties by way of motorised limbs, using a technique called 'targeted reinnervation'. Pioneered by Dr Kuiken, director of the Neural Engineering Centre for Artificial Limbs at the Rehabilitation Institute of Chicago, this procedure involves taking the nerves that would have originally controlled the arm or leg and rerouting them instead to other parts of the body. By rewiring a missing arm's motor nerves to muscles in the remaining stump, shoulder or chest, for example, and rewiring the arm's sensory nerves to the skin in these regions, a channel is opened to the part of the brain that once controlled the missing limb.

Targeted reinnervation is a strange and slightly ghoulish idea, because it means that if a patient tries to flex his missing finger, for example, a muscle in another part of his body (which is now connected to the nerves that used to control the finger) contracts instead. “When the amputee wants to open or close their hand, these muscles twitch,� says Dr Marasco. EMG sensors detect these signals and translate them into control signals that cause the mechanical hand to open and close. The patient can then open and close his prosthetic hand simply by trying to move the fingers that are no longer there.

The applications are endless, and raise the question, what will happen when what we build is better than what we were before?

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Hannah Pook

The Genetics of Breast Cancer Every year nearly 58,000 people are diagnosed with breast cancer in the UK, the equivalent of one person every 10 minutes. One in eight women in the UK will develop breast cancer in their lifetimes. Clearly, breast cancer is, despite continuing research, one of the most prevalent and potent diseases known to us.

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ancer itself is a genetic disease, caused by genes that control the way our cells function and especially how they grow and divide. Mutations in these essential genes lead to uncontrollable cell division and hence cancer. These mutations can either be germline, present in egg and sperm cells and hence inherited from parents, or somatic – changes which are acquired in our lifetime and not passed on to children.

It is my belief that through understanding the genetics of breast cancer we can create new treatments, more personalised for patients, helping them to recover more quickly and with fewer side effects.

So which mutated genes are associated with breast cancer in particular? So far, about 26 mutated genes have been linked to breast cancer, the most well-known of which are the BRCA genes. These two genes alone account for 20 to 25% of hereditary breast cancers and 5 to 10% of breast cancers overall. 55-65% of women with a BRCA1 mutation and 45% of women with a BRCA2 mutation develop breast cancer before the age of 70, compared to just 12% in the general population who will develop breast cancer at some point in their lives.

The BRCA mutations are germline mutations (passed down from parent to child) causing hereditary breast cancers.

The two mutated genes are both autosomal dominant, meaning that the risk of breast cancer increases when only one copy of the mutated gene is inherited and that the genes are found on one of the numbered, non-sex chromosomes – so whether you are a boy or a girl does not affect your chance of inheriting the mutated gene.

In order to understand how these two genes lead to breast cancer once mutated it is first important to understand their normal structure and function.

The BRCA1 gene is located on chromosome 17 and BRCA2 on chromosome 13. Although initially thought to work by coding for tumour suppressor proteins, both actually work by coding for proteins which are essential to a type of DNA repair.

Not much is known about the structure of the BRCA1 protein, but it is known to have a RING domain and 2 BRCT domains which have been implicated in several protein-protein interactions.

The BRCA2 gene codes for a 3418 amino acid protein which has 8 BRC domains, allowing the BRCA2 protein to interact with the monomeric RAD51 protein.

So what do the two proteins actually do? As expected, both proteins take part in an enormous number of pathways in the

cell, each carrying out a large number of functions. Their most documented role and the role most integral in preventing the formation of cancers is DNA repair, which is what I will focus on.

The two proteins are thought to be involved in a method of double stranded DNA break repair known as homologous recombination (a type of homology directed repair). This is a method in which the repair apparatus consults the homologous DNA sequences in a sister chromatid and then uses those sequences as a template to repair the DNA break.

Homology directed repair begins with the resection (removal of DNA) by an exonuclease of one of the two DNA strands at each of the ends formed by a double stranded DNA break. The exonuclease involved is likely to be the MRN complex.

The next step is for each of the resulting single stranded DNA strands to invade the undamaged sister chromatid, which has had its double helix unwound in order to accommodate the pairing of the invading single stranded DNA strands with complementary sequences in the undamaged sister chromatid.

After this the ssDNA strands are elongated by DNA polymerase, using the strands of the sister chromatid’s DNA as templates.

The extended ssDNA strands are then released from the sister chromatid and caused to pair with one another, allowing further elongation by a DNA polymerase. Finally, a ligase works with the DNA polymerase, reconstructing the double helix.

So where do BRCA1 and BRCA2 fit into this process?

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Hannah Pook

ATM protein is able to catalyse the transfer of a phosphate group from ATP to other molecules, including H2AX. The phosphorylated H2AX attracts the BRCA1 protein to the double stranded break. The BRCA1 protein is then also phosphorylated by ATM. BRCA1 serves as an anchor and coordinator of the following events and likely binds to the DNA itself via a region in the middle of

BRCA1 and BRCA2 are both able to bind t o a large number of different proteins, many of which are known to be involved in DNA repair. Therefore, the BRCA proteins are thought to act as scaffolds to assemble repair proteins into the complexes needed for homologous recombination. One of the most interesting things on BRCA1 is the large number of phosphate groups that can be attached to it. It is likely that BRCA1 can bind to so many different proteins because each time a phosphate group is added in a different location it changes the conformation (the shape) of the BRCA1 protein.

However, between the double stranded DNA break occurring and BRCA1 and BRCA2 starting to carry out their functions several other processes have to take place.

First of all, the double stranded break has to be recognised by the MRN complex (MRE11, RAD50 and NBS1).

The MRN complex then activates ATM kinase function, which means that the

the protein, roughly amino acids 450-1110.

The MRN complex resects the DNA to form overhangs that are bound by RPA, forming substrates for a protein called RAD51.

The MRN complex is able to bind to the BRCA1 protein via RAD50. It has been shown in recent studies that BRCA1 inhibits the exonuclease activity of the MRN complex, which may help to stop the complex from breaking down too much of the DNA. PALB2 binds to both BRCA1 and BRCA2, acting as a bridging protein and recruiting BRCA2 to the site of repair. The BRCA2 protein then interacts with RAD51 molecules, joining them together into long strings, allowing them to be loaded

onto the RPA-coated DNA. When RAD51 binds to the DNA it forms a nucleoprotein filament which is able to search for DNA sequences similar to that of the overhang, leading to strand invasion and the subsequent steps of homologous recombination.

Without the functioning BRCA proteins homologous recombination would not be able to take place.

So what happens when the BRCA1 or BRCA2 genes are mutated? The genes would no longer code for the same proteins and most commonly a truncated (or shortened) form of the protein is produced. As the primary structure of the protein is different, the tertiary structure is also altered. With different domains, the BRCA1 and BRCA2 proteins cannot interact with the other proteins necessary for homologous recombination. In the absence of homologous recombination, another, more error-prone method of fixing double stranded DNA breaks is employed, known as non-homologous end joining. When the genes are incorrectly fixed it leads to mutations, some of which can lead to cancer.

But how is all of this information actually useful to us?

One way it aids us is to help identify new drugs for treating cancer.

PARP inhibitors are a promising new set of drugs which take advantage of the fact that BRCA mutated cells cannot repair DNA through homologous recombination. The PARP enzymes (Poly (ADP-ribose) polymerases) are involved in repairing single stranded DNA breaks and when they are inhibited single stranded DNA breaks are not repaired. During DNA synthesis the replication forks collapse, forming double stranded DNA breaks which cannot be fixed by homologous recombination and have to be repaired by non-homologous end joining (a more error prone method).

Eventually accumulated mutations in the DNA of the cancer cells trigger apoptosis, killing them. This is a clear example of how through understanding the genetics behind cancer we can create better therapies, improving treatment for thousands. The first PARP inhibitor, known as Olaparib, was approved by the NHS for use in the UK on the 11th of December 2015.

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Hearing Vladimir Kalinovsky

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earing, auditory perception, or audition is the ability to perceive sound by detecting vibrations (changes in the pressure of the surrounding medium through time) through an organ such as the ear. The ear has 3 main sections: Outer, Middle and Inner and the sound travels from the outer to the inner ear.

The Outer Ear consists of the pinna and the auditory canal. The function of the pinna is to reflect sound waves towards the auditory canal. It also helps us to orientate due to its anatomy. The pinna largely eliminates a small segment of the frequency spectrum; this band is called the pinna notch.

The pinna works differently for low and high frequency sounds. For low frequencies, it behaves similarly to a reflector dish, directing sounds toward the ear canal. For high frequencies, however, its function is thought to be more sophisticated. While some of the sounds that enter the ear travel directly to the canal, others reflect off the contours of the pinna first: these enter the ear canal after a very slight delay. This delay causes phase

cancellation, virtually eliminating the frequency component whose wave period is twice the delay period. Neighbouring frequencies also drop significantly. In the affected frequency band – the pinna notch – the pinna creates a band-stop or notch filtering effect. This effect is actually what helps you to locate the sound in a corner as our brain makes very slight comparisons that we sometimes even do not recognize.

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As the sound travels along the auditory canal it then reaches the tympanic membrane or ear drum. If the sound pressure waves in the air were applied directly to the inner ear fluid, 99.9% of the accoustic energy would be lost because of their reflection at the air/fluid interface. Therefore another mechanism is required.

The middle ear acts as a pressure amplifier: in this way it is able to 'capture' the available acoustic energy in the air.

The pressure, in this case, is sound and it causes the tympanic membrane to oscillate. The three smallest bones in the body, known collectively as the ossicles which include the malleus, incus and stapes (sometimes referred to colloquially as the hammer, anvil and stirrup respectively) are connected to the tympanic membrane and acts as a sound amplification mechanism. As sound waves vibrate the tympanic membrane (eardrum), it in turn moves the nearest ossicle, the malleus, to which it is attached. The malleus then transmits the vibrations, via the incus, to the stapes, and so ultimately to the oval window, the opening to the vestibule of the inner ear.

The Inner Ear consists of the cochlea, which is an ink sackspiralshaped, fluid-filled tube. It is divided lengthwise by the organ of Corti, which is the main organ of mechanical to neural transduction. Inside the organ of Corti is the basilar membrane, a structure that vibrates when waves from the middle ear propagate through the cochlear fluid – endolymph. There are

fluid-filled spaces on each side of the cochlear partition, named the scala vestibuli and the scala tympani; a distinct channel, the scala media, runs within the cochlear partition. The cochlear partition does not extend all the way to the apical end of the cochlea; instead there is an opening, known as the helicotrema, which joins the scala vestibuli to the scala tympani. As a result of this structural arrangement, inward movement of the oval window displaces the fluid of the inner ear, which causes the round window to bulge out slightly and deforms the basilar membrane which has an important function in our hearing process. The basilar (tectorial) membrane is tonotopic, so that each frequency has a characteristic place of resonance along it. Characteristic frequencies are high at the basal entrance to the cochlea, and low at the apex. Basilar membrane motion causes depolarization of the hair cells, specialized auditory receptors located within the organ of Corti. While the hair cells do not produce action potentials themselves, they release neurotransmitter at synapses with the fibres of the auditory nerve, which produce action potentials. In this way, the patterns of oscillations on the basilar membrane are converted to electrical signals firings which transmit information about the sound to the brainstem.

The hair cells play a key role in converting the sound waves into electrical impulses.

In mammalian outer hair cells, the receptor potential triggers active vibrations of the cell body. This mechanical response to electrical signals is termed somatic electromotility and drives oscillations in the cell’s length, which occur at the frequency of the incoming sound and provide mechanical feedback amplification. Outer hair cells are found only in mammals. While the hearing sensitivity of mammals is similar to that of other classes of vertebrates, without functioning outer hair cells, the sensitivity decreases by approximately 50 dB. Outer hair cells extend the hearing range to about 200 kHz in some marine mammals. They have also improved frequency selectivity (frequency discrimination), which is of particular benefit for humans, because it enabled sophisticated speech and music.

The effect of this system is to non-linearly amplify quiet sounds more than large ones so that a wide range of sound pressures can be reduced to a much smaller range of hair displacements. This property of amplification is called the cochlear amplifier.

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Vladimir Kalinovsky

The molecular biology of hair cells has seen considerable progress in recent years, with the identification of the motor protein (prestin) that underlies somatic electromotility in the outer hair cells. Prestin's function has been shown to be dependent on chloride channel signalling. This leads to the contraction of outer hair cells by somatic motor and it leads to the contraction of basilar membrane resulting in the sound amplification. Research is still currently being done.

Inner hair cells are the most vital part of our ear as their main role is to convert sound kinetic energy into the electric energy so information can pass to the our brain. This is called mechanoelectrical transduction and occur by the deflection of the hair-cell stereocilia which opens mechanically gated ion channels that allow any small, positively charged ions (primarily potassium and calcium) to enter the cell. Unlike many other electrically active cells, the hair cell itself does not fire an action potential. Instead, the influx of positive ions from the endolymph in the scala media depolarizes the cell, resulting in a receptor potential. This receptor potential opens voltage gated

calcium channels; calcium ions then enter the cell and trigger the release of neurotransmitters at the basal end of the cell. The neurotransmitters diffuse across the narrow space between the hair cell and a nerve terminal, where they then bind to receptors and thus trigger action potentials in the nerve. In this way, the mechanical sound signal is converted into an electrical nerve signal. Repolarization of hair cells is done in a special manner.

The perilymph in the scala tympani has a very low concentration of positive ions. The electrochemical gradient makes the positive ions flow through channels to the perilymph.

Hair cells chronically leak Ca2+. This leakage causes a tonic release of neurotransmitter to the synapses. It is thought that this tonic release is what allows the hair cells to respond so quickly in response to mechanical stimuli. The quickness of the hair cell response may also be due to the fact that it can increase the amount of neurotransmitter release in response to a change as little as 100ÂľV in membrane potential.

Conclusion As you may have spotted, hearing is a very complex process and there are many things yet to be discovered. Nowadays, the hearing process is underestimated by many people. Without it, there wouldn’t be us, we would have become extinct thousands of years ago. Our ancestors, Cro-Magnon (European Early Modern Humans), wouldn’t have developed a stable society of huntergatherers and they wouldn't have a beginning to the species that changed the entire planet. We invented letters, languages, investigating the world around us and inside us, we built the first spaceship, we have been on the moon and are even planning to colonize another planet. There are many examples in wildlife of blind animals with outstanding hearing; however, very few of them with good sight, but poor hearing. I hope you found my article interesting and may have discovered something new.

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Alice Fish

Pigmentation of Dinosaurs For the first time in science, humans have been able to judge the colour of certain extinct animals by looking at well preserved fossil remains.

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hey did this by looking at the amount of melanin or melanin traces there are in these fossils.

Melanin is the most abundant pigment in animals. The three types of melanin I will be discussing are eumelanin, which causes brown and black colouring in abundance and yellow/grey in lower concentrations; pheomelanin which causes red brown colours in abundance and reds and oranges in lower concentrations; finally sepiomelanin, derived from eumelanin is the pigment used in the ink of cephalopods such as cuttlefish.

The University of Manchester tried to look at the possible colouring of a 120 million year old Confuciusornis sanctus, an extinct bird. By using a synchrotron, a powerful x-ray source they could observe the pigment eumelanin, by using copper as the trace marker. This meant that areas with high amounts of eumelanin, and therefore copper, appeared lighter as fewer of the X-rays were absorbed. This allowed the scientists to create a monochrome picture of the bird. The pigments also could help reveal clues about the chemical reactions that took place in their bodies, as well as the food which fuelled those reactions.

Researchers have inferred the colour of fossilised creatures by looking at the structure of melanosomes within fossils. As you can see in figure 2 there are indentations in the fossil. These are believed to be melanosomes, but some people say these sausage-shaped and spherical bodies are much more likely to be keratinophilic bacteria which would have coated the fossil, as they secrete the enzyme keratinase to digest the keratin found in hair and feathers. There is evidence that the microstructures are found in Jehol fossils (found in the Jehol beds in north east China). Firstly the melanosomes are embedded in the β-keratin matrix and not just superficially coated like the bacteria would be, as the

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fossil has acted like a mould showing the shape of the melanosomes (as shown in the picture).

This occurs most commonly in dinosaurs and birds in the Jehol group.

Also the microstructures occur in bands and stripes, this regular structure suggests they are melanosomes, as bacteria would be arranged randomly. In 2009 it was show that a fossilised feather would have been iridescent, as stacked melanosomes created light-refracting surfaces.

Dinosaurs and feathers Before the 1990s the origin of feathers was highly debated until the Archaeopteryx lithographica (the world’s oldest bird) was found with preserved feathers, resembled theropod dinosaurs and so evidently derived from them.

The Sinosauropteryx was found in the Jehol group with protofeathers (also known as dino fuzz) preserved.

Since then more theropod dinosaurs have been found with both feathers and protofeathers.

A 160 million year old ink sac from a cuttlefish-like animal contained the soft pigment sepiomelanin, not just microstructures and provided soft tissue specimens. This ink was very similar to modern squid ink, suggesting this defence mechanism has not changed much since the Jurassic period. Mass spectrometry was used to measure the masses of individual molecules, allowing the identification of sepiomelanin in the fossilized ink sac. Being able to look at pigments and soft tissue samples gives another set of information on top of skeletal information which palaeontologists rely on heavily.

McNamara was sceptical about the accuracy of Vinther’s colour assignment using the imprint of melanosomes. She recreated the process of fossilisation by putting modern bird feathers in an autoclave (used to sterilize lab equipment). It created 250 atmospheres of pressure and heated to 250°C, a small amount of time in this machine simulates the effects of pressure and temperature over millions of years. After this process the melanosomes under the highest temperatures shrank by 20% in width and 19% in length. The percentage change depends on the preservation of the fossils - if they were from hotter and deeper deposits, they would be more distorted.

Vinther knew that melanosomes become smaller during fossilisation, and adjusted this for a later paper finding that it had little effect on the colours, and would only have an effect when trying to distinguish between two similar colours.

If you were to look at the fossil of Anchiornis huxleyi you would see a high concentration of spherical microstructures, as pheomelanosomes are spherical (contain pheomelanin), showing that there is a bright red-brown colour, there would be no melanosomes in the white banding, and high concentrations of sausage-shaped microstructures on the black parts with a lower concentration on the grey body and tail, as eumelanosomes are sausage-shaped and contain eumelanin. Here I have worked backwards but this should give a better idea of how it is applied.

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Raymond Ho

Parkinson’s

A poet would say Parkinson’s is a beautiful disease, ripping away the fundamental ability of movement and communication, leaving only shards of imagination and memory as remnants. Scientists, however, would like to think that Parkinson’s is an interesting disease. How can the deficiency of one small, charged molecule – dopamine- lead to such a big change? Why is it lost in the first place? Is there any way we can even approach this problem?

Read on to find out more…

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t would be fair to say that Parkinson’s (PD) is a dodgy disease. We do not know enough about the brain to conclude any significant causes of Parkinson’s, nor can we suggest any miracle drug that can cure Parkinson’s with no side effects. Is there really no approach to this tragic disorder which is affecting more than 127,000 people in the UK? Obviously not, or I wouldn’t be writing this essay…

Firstly, let’s look at symptoms and clinical diagnoses of Parkinson’s. The most common clinical definition of PD is having bradykinesia in addition to one of the following: Dystonia, hypokinesia and tremor.

A simplified explanation of these fancy terms would be as follows: Bradykinesia is slowness in performing common voluntary movements, for example, walking, eating, writing, etc.

Dystonia is a rigidity of muscles that give way in little jerks or 'cogwheels'.

Hypokinesia is a severe impairment in generation of movement. A tremor is the rhythmic shaking of the hands, sometimes the feet, it is also why the original name of PD 'shaking palsy' was called so by surgeon James Parkinson.

However, the main problem of PD is not at the muscles, which are still working fine, nor is it at the thought of moving the muscles, but the link in between.

To understand how lack of dopamine can lead to symptoms seen above, we need to look at how dopamine functions in the body.

A structure in the brain called substansia nigra pars compacta (SNc) in the basal ganglia takes a vital role in occurrence of PD because it contains dopaminergic neurones which are responsible for the synthesis of the allimportant dopamine molecule, of which PD is said to result from the lack of.

Many of the dopamine neurones (DA) in the substansia nigra are connected to the striatum, which forms a pathway called nigrostriatal pathway. The role of dopamine in SNc is complex, it does not directly stimulate movement: instead, it regulates the striatum, contributing to fine motor control. But how exactly does it work? Let’s look at what happens to a dopamine molecule in the brain.

The Story Of A Dopamine Molecule In the substansia nigra, tyrosine (which is found in protein-heavy foods like seaweed, salmon, eggs, etc.) is converted into L-DOPA through the action of tyrosine hydroxylase.

L-DOPA is then converted to dopamine via DOPA carboxylase. Dopamine molecules are stored in synaptic vesicles in the neurone. When an action potential is travelling through the axon to the synapse, it triggers exocytosis, where dopamine vesicles bind to presynaptic membrane.

Hence, dopamine can be released into the synaptic cleft. Some dopamine molecules may bind to receptors on a receiving neurone. For details please

see the diagram below. What happens in synaptic cleft? This action triggers a signal that is relayed through neurones to the motor centre in the cerebral cortex

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of the brain. The signal eventually travels through the spinal cord to affect activity in muscle cells. Note that free floating dopamine molecules substantia in the synaptic gap can be taken back to the neurone by specific protein channels on the presynaptic membrane, where it can be packed and re-used, or can also be converted to other substances like Monoamine oxidase (MAO) or CatecholO-methyltransferase (COMT).

Why Blame Dopamine?

What is Happening During Pd?

Diagram of Fenton Reaction

Most websites talking about Parkinson’s Disease explain that PD is caused by lack of the neurotransmitter dopamine.

However, almost none of them explain why the lack of dopamine will lead to Parkinson’s. One way of looking at Parkinson’s is not from a dopamine molecule’s perspective, but from the balance between dopamine and another neurotransmitter- Acetylcholine (Ach).

The balance between Ach and dopamine will be upset due to lack of dopamine. Generally speaking and extremely simply; Ach stimulates muscle contraction while dopamine stimulates the striatum, which indirectly sends an inhibitory signal. When there is lack of dopamine, there will be lack of inhibition in the striatum, and high levels of Ach. These two factors combined will lead to excessive muscle contraction.

Of all the symptoms, the tremor may be the least explicable, because Parkinson’s Disease is always characterized by an inability to initiate movements which is caused by an inhibition of the contraction of muscles, while a tremor is caused by excessive muscle contraction. How can this seemingly contradictory event occur? It is because there is always a motor signal in the background to maintain our body posture, and the lack of inhibition to striatum will lead to insufficient screening of excessive motor signals, which will in

turn cause a tremor.

So why exactly do DA die? A plausible hypothesis could be due to the breakdown of dopamine. All neurotransmitters have to be removed in some way, as they can’t stay in the receptors forever. But unlike normal neurotransmitters, the metabolism of dopamine will yield a by-product: hydrogen peroxide (H2O2). H2O2 rapidly dissociates to form radicals. By The hydroxyl radicals produced are lethal to the neurone as it disintegrates the membrane. Dead neurones cannot be revived. Dead DA stay dead. So the loss of dopamine in the brain is permanent.

However, there are actually changes in the brain to help compensate for the loss of DA. Neighbouring DA will produce more dopamine to try to compensate for the loss. Researchers have now also found that norepinephrine may be responsible for regulating activities of dopamine neurones, which stimulate surviving dopamine cells to increase activity and output of dopamine.

(BBB), which has specific conditions for different molecules. In other words, it is selectively permeable.

On the one hand, dopamine carries a charge due to the creation of a zwitterion, it is not lipid soluble and there are no carrier proteins specific to dopamine in the BBB, and hence it cannot cross the BBB. On the other hand, L-DOPA, the precursor dopamine does not form a zwitterion and has a specific protein carrier in the BBB. Hence L-DOPA is able to pass through and deliver the much-needed dopamine. But there is still a slight problem. L-DOPA is being converted to dopamine outside the body before it can reach the brain. What is our tactic? Same old trick, we inhibit the enzyme responsible, DOPA decarboxylase, by using a chemical called Carbidopa.

Frontiers Of PD Now, let’s talk about potential approaches to this difficult problem of PD. Not surprisingly, one main way to combat the lack of dopamine is to increase the levels of dopamine in the brain. And we can do this through various methods.

In order to enter the brain, every drug has to pass through the blood brain barrier

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Raymond Ho

Carbidopa

'Old trick' Carbidopa is designed to work outside the brain, as its structure does not allow it to pass through the BBB. Hence, L-DOPA is now protected whilst outside the brain, but can convert to the scarce dopamine inside the brain.

The levels of MAO, the enzyme which oxidizes dopamine (and produces radicals in the process), increase with age. This may be one of the reasons why PD symptoms are mostly seen in old age (>50). Another factor that can affect dopamine is oxygen levels. When there is a lack of oxygen in SNc, less energy will be available to the neurone in the form of ATP. Hence, processes like the re-uptake of dopamine cannot occur. This will lead to the breakdown of more dopamine molecules by MAO, producing more hydroxyl radicals.

A way to prevent this is to inhibit the enzyme MAO. There are two obvious benefits to this strategy, the valuable dopamine can be conserved to fulfil its normal role in control of movement and the production of toxic free radicals can be reduced. MAO inhibitors are now considered as a class of drug comparable to the well-established therapy of L-DOPA. Nonetheless, an understanding of PD cannot hinge around dopamine alone, but how it interacts with other systems. The balance of Ach, glutamate with dopamine

are vital to the symptoms of PD. Apart from chemical systems, we can also shift our gaze to nilotinib, which was alledged to clear α-Synuclein accumulated in the brain. α-Synuclein are proteins that are thought to trigger the death of brain cells like DA. Researchers believed the drug was very effective, but no firm conclusions can be drawn until the drug has been tested in a larger trial with a placebo. Moreover, the drug costs more than $100,000 and so is unattainable for the majority of the population.

Just for a moment, let’s go back to the dopamine molecules. What I am about to suggest is not scientifically proven at all; however, I would still like to raise this point in the hope that I or

one of you reading this magazine can help us find the answer. Apart from being a chemical that regulates movement, dopamine is also a main neurotransmitter in the reward channel. Consider that when people are happy, the production of dopamine in another area called ventral tegmental area (VTA) increases.

Could this increased level of dopamine be any use to us? I believe that in nonPD patients, this will reduce the risks of Parkinson’s Disease, while in PD patients, this may prevent the symptoms from drastically deteriorating. It would be very ironic if this were true. We spend countless amounts of money on research and drugs only to find that the best drug we have may be free, or perhaps priceless.

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CLU B S

Medics Club

First Year Chemistry Club

Chemistry Extention Club Review

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t’s been a great first year for Medics Club. Founded just at the beginning of the year, the newest addition to the school’s numerous science societies regularly attracted over twenty members for sessions every Wednesday lunchtime.

After some debate, the club’s founding committee settled on a format in which members prepared presentations on current medical issues such as HIV, heart attacks and Ebola and then led a passionate debate on questions related to the topics. Often controversial, the sessions culminated in a vote to decide which side had won the argument, sometimes with surprising results. On one occasion half the club decided that when funds were limited we should not treat Alzheimer’s patients, as the money could be better spent elsewhere. This is a clear example of the difficult, and sometimes controversial, decisions that the NHS has to make in real life.

Medics Club also provided aspiring 46 medics with helpful advice and an opportunity to learn more about life as a doctor, organising a trip to the Royal Society of Medicine in London for a day entitled ‘So you want to be a doctor?’ and working with the school careers advisor to arrange work experience at Epsom Hospital during the Easter holidays. The club also hosted a session by current Upper Sixth pupil, Eva Wang, who talked about her own recent experience of the BMAT entrance exam. It has been a privilege to set up and run Medics Club and I very much hope that the success continues into next academic year.

his academic year has seen the start of an exciting new Chemistry Club, open to all keen scientists in the First Year. The club has proven very popular, with many students attending each week to take part in some exciting science experiments. The club allows the students to carry out some off syllabus experiments, just for fun, offering the opportunity to get hands on with scientific equipment, investigating some of the interesting science in our world; many of the experiments are things you would be able to carry out at home!

One of the most popular experiments was making slime with very unusual properties, closely followed by crystal growth from saturated solutions of sugar. We have not been limited to chemistry however; the students recently investigated the visible light spectrum by making some colour wheels and also used static electricity to make some tissue paper ghouls dance! We are looking forward to our final term of experiments, who knows what exciting discoveries we might make!

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his has been a spectacular opening year for the recently reformatted Chemistry Extension Club. The goal of the club was to learn about interesting aspects of chemistry through a series of mini laboratory projects, the content of which was not included within the A Level syllabus.

The most popular project, which spanned over a number of weeks was the complex and challenging synthesis of aspirin; the students loved applying their knowledge of organic chemistry, and being able to use the advanced melting point apparatus to identify the compound and confirm its purity. It was fantastic to see the enthusiastic students rise to the undergraduate level challenge and do so with such style.

Other highlights from the year include the students mastering alchemy, turning a copper penny into a ‘gold’ coin, and their creativity shone through when challenged with making glass sculptures. It has been a phenomenal first year for the club and next year promises to be even bigger and more ambitious.

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Anatomy Club F

inding its way into the Biology department at the start of 2015 came the Anatomy club. It is dedicated to introducing and educating students in younger years to certain species that would otherwise perhaps stay unknown to them. Thomas Land and Emily Yates each took a presentation and organised the subsequent dissection for the two organisms investigated. The first dissection was the Common Dogfish while the most recent examination was the Jumbo Frog. However amusing its name, these organisms are perfect for finding out how all frog anatomy works and is so different from anything we had seen before in a school lab. Seeing students from Third Year to Sixth Form excited and inspired really drives home what the club is about. I can only hope that the club continues to flourish and grow from 2016 onwards.

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t the end of the previous academic year the Parents Association kindly funded the purchase of a huge supply of LEGOTM Mindstorms equipment. This is based on regular Lego technic but is also programmable via the students' iPads. This has provided an amazing learning opportunity that has been used throughout the year. Notable lesson highlights include a group of Second Year students (Shreya Kumar, Alex Auletta, Ellen Carmona, Husayn Moosa & Seb Ahmed) creating an autonomous parking vehicle. The LEGOTM club has run on Tuesdays throughout the year and has been host to a huge turnout of over 30 keen pupils. Their initial challenge to create race cars caused them to create and design power train systems and sensitive steering mechanisms. Congratulations go to Yuka’s team for creating a simple solution to the problem and blasting to victory.

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S CI E N C E T RIPS

Down House Thomas Land

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ate in 2015, the Sixth Form Biology students got the chance to visit Down House, the home of one of the most influential men in science to have ever lived, Charles Darwin. He lived here for 4o years with his wife Emma from 1842 to his death in 1882. For me, a great fan of his revolutionary book, On the Origin of Species, this was an exciting chance to see into the life of the great man. It began with the coach dropping off the students in the small village of Downe, and our first stop was the church.

This was the church which the Darwin’s attended for so many years before Annie, his beloved daughter died aged 8. At that point his belief in God faltered and

he stopped attending, even being buried in Westminster Abbey. We managed to find the grave of his family and paid our respects before walking up the lane to the house itself.

In the morning, we had a great three storey house to explore with a headset and Sir David Attenborough’s melodious tones explaining the details of Darwin’s life. Upstairs contained some of his original notes and most treasured of all, a first edition of On the Origin of Species locked away behind thick glass walls.

The afternoon took us outside into the gardens to see the love and care put into both the flower garden by Emma, his wife, and the greenhouses by Charles. With

the sun shining down you could almost begin to imagine life 150 years ago in the grounds of the estate. For those of us who were watchful, we found the so-called ‘Thinking Path’ along which Darwin pondered his great theories of evolution and whether he dared publish his book that went against the Church's teachings.

Finishing the day with a cream tea, I could reflect on the day and what I had learned about the man, about his conflicts, his problems and his theories (all of which were absolutely fascinating).

This trip was a real treat for anyone, from those who have only ever heard of Charles Darwin to an avid follower of his books and theories.

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St Peter's Oxford Trip Nikita Komarov

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ot for a second were we displeased about the 5am start on a Wednesday morning as we were all ecstatic to get on a coach to Oxford. When we arrived, the five of us were overwhelmed by the beauty of the town. Little did we know, the inner workings of the university were even more exciting.

Having spent the morning in the science department, listening to talks and walking tours of our subjects, any doubts which previously stood in regards to the question of whether we wanted to come here were eliminated.

St Peter's itself is a gorgeous college, which we discovered as soon as we saw it. Incredibly cosy but in no way cramped, the college immediately struck a chord with us. We marvelled at the students and the facilities before cramming into the Dorfman Centre to hear Professor Jan Schnupp performing a mock interview. We listened intently, as it was invaluable for us, as future candidates, to hear the format of what will be one of the most important conversations of our lives. Later that day, we were given an opportunity to have an exclusive meeting with Dr Robert Pitkethly, the admissions officer at St Peter's. This was, perhaps, one of the most important meetings any of us have had, as it gave us an opportunity to ask incredibly specific questions about the application process, interview, admittance, as well as general settlement of any doubts or fears which any of us may have had. The same evening was then spent undergoing some of the most intense brain training, where we presented our researched topics to not only an audience of our peers, but also Mr Quinton, Mr Keyworth, as well as two Old Cats and current Oxford students, Duke Quinton and Glenn Gowers. It was very thrilling to receive both praise and criticism as it is always incredibly valuable not only to know what you do well, but also to know what you can improve. It was clear that we all had a long way to go to but we were motivated to put our hearts and souls into the Oxbridge training programme.

Our accommodation was the New Block of St Peter's, which was very much comparable to a hotel, and we settled in for the night, having learned so much that day. In the morning, we ate in the dining hall at St. Peter's, and eagerly rushed back to the Dorfman Centre to hear Jan Schnupp deliver a presentation titled 'An introduction to Neuroscience'. We listened

intently as Jan explained the complexity and the incredible interconnectivity of the brain and its components. We learned about ion channels, neurons, the ear and more. Then came time for some questions, of which we had all built up a list. Having chosen the best ones, we put our hands up and, as expected from a group of Cats, dominated the session with both interesting and complex questions, all of which must have made the rest of the audience rather embarrassed. Having thanked Professor Schnupp, as well as clarified some follow-up queries about his talk, we again sat down for an intense session of discussion, where we all learned yet more about lateral thinking, and prepared for the long journey which lay ahead of us.

Overall, it was an invaluable experience which has made us fall in love with the University, as well as giving us an opportunity to understand what we need to do in order to have a shot at settling down at Oxford at the end of our school careers. We would like to thank Mr Quinton and Mr Keyworth for organising such a fantastic trip; Duke Quinton and Glenn Gowers for being incredibly helpful and motivating during our training sessions; as well as all the staff and students at St Peter's who welcomed us with open arms and dedicated hours to answering our questions and making our time as pleasing as possible.

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Camber Sands Nikita Komarov

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n a sunny summer morning, we piled into a coach to take a leisurely drive to the lovely beaches of Camber Sands. To start off, we split into groups to learn about succession and the various types of species which reside on the land around the beach. It is always invaluable to learn about certain topics by physically eyeballing the concepts, in this case how the different species of plants refuse to live alongside each other nicely.

After our study session, we then split into groups again, this time to collect

some data of our own. We had only heard stories about the amazingly brutal experience that was to come.

There are certain things one isn’t told about physical learning, one of them is that there is almost no limit to what you can be expected to do. As we looked over the strip of land we were expected to investigate succession on, we didn’t know whether to laugh or to cry. But we soldiered on. Some of us picked the short straw, and had to wade through the treacherous bushes of sea buckthorn.

With thorns sticking into every exposed

piece of skin, we trudged on to get the data we needed. Once we collected information we desired about the plants, we headed back to the beach, where some of us had the pleasure of going for a brisk dip in the ocean.

Overall, it was a priceless experience where we managed to solidify all of our knowledge on succession. Once again it has been shown that methods of teaching at Caterham School go above and beyond what is required, and the exam results go on to prove this fact.

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Science Week

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very year, the school celebrates British Science Week, putting on incredible science shows and amazing assemblies. This year, we had a wealth of science exhibitions including the annual assemblies taken by myself and Tom and my personal favourite assembly of the year, the chemistry extravaganza, put on this year by a great team of Upper Sixth chemists. The awe and wonder on the faces of the 400 Prep School pupils, crammed into the Rudd Hall, as the team lit up the stage with an absolutely outstanding fire show (and of course the very exciting Elephant Toothpaste experiment), just reminded me of my all the reasons I wanted to learn about science. Thanks to Mr Keyworth and Miss Pilkington for all the help on this year’s show and good luck to all the teams of the future. I hope you inspire many more budding scientists to take up this utterly extraordinary subject.

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Camber Sands

Dale Fort 2015

Nikita Komarov

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o trip is better known in the science department than the Dale Fort Biology Field Trip. For five days, Upper Sixth Form pupils better acquaint themselves with the Pembrokeshire coastline in Wales. With our feet having only just touched Welsh ground, we were whisked into the library with our excellent guide to Dale, Steve, for an introduction to the fort before heading out to the shores for a preview of our time there to come.

Over the next few days, we studied species diversity and population size, taking belt transects over the beaches at low tide and digging around for sandhoppers, never seen leaving the fort without an abundance of quadrats, rulers and clipboards. Back inside, the calculators were whipped out as the age old debate (T-test or 95% Confidence Limits) raged on in our statistical test

lessons with Mr Quinton and Mr Marlow, some even lasting until 11pm.

On the third day of our trip, we embarked on the 5km Great Salt Marsh Run, with Milly Berry and Alex Craston securing two spots on the new winner’s board in the Biology department.

Sunglasses were undeniably a necessity as we walked out to the Salt Marsh for the second time that day, observing unmistakable evidence of succession, and scouring the lake for crabs and fish. Setting off at 11.30pm, a small group studied the movement of limpets along the jetty. Apparently static and immovable, we were astounded by the immense distances they had moved, having marked them only that afternoon.

Having managed to persuade our nighttime guide, Kim, to take us to see the plethora of sea life in the rock pools and deeper shores, we headed back to our

dorms at well past midnight, ready for the next day.

On our penultimate day, small group projects were launched. From the diet of sea anemones to the colour of flat periwinkle shells, everyone seemed inspired by the stunning coastline. That night, the sky was lit up with Chinese Lanterns, each group scribbling wishes onto their lamps before releasing them out towards the sea. We ended on a high the next morning, taking a speedboat round the coast, past sight of the fort. Collecting hundreds of different kinds of plankton, we examined them under the microscope. Steve’s running commentary on the varieties served as a brilliant soundtrack as the weird and wonderful creatures moved around on the slide.

On the whole, it was an incredible week, one I’m sure many will never forget.

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Science Week

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Badges

In previous years, our prestigious speakers have been given gifts as a memento and a sign of thanks for their hard work and contribution to the society. This year, Tom and I wanted to add something that would allow our speakers to stand out as MJS alumni and while the classic hot pink ties and t-shirts are undoubtedly popular, we knew it would be difficult to wear them every day.

And so, the inspiration for the Moncrieff-Jones badge

was born. We aimed to design a simple and classic look to reflect the age and stature of the society with a touch of the Moncrieff-Jones signature colour and the MJS motto, 'Teaching through Wisdom' stamped proudly underneath. We wanted to show our appreciation for the determination and bravery all our speakers have given to the society and we hope this precedent will be emulated for many years to come.

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Past Moncrieff Presidents, Vice-Presidents & Endorsers

2007-2008 President Luke Bashford (University College London) Vice President Edd Simpson (University of Leeds) 2008-2009 President Tonya Semyachkova (Balliol College, Oxford) Vice President Raphael Zimmermann (University East Anglia) 2009-2010 President Alex Hinkson (St Catherine’s College, Oxford) Vice President Alexander Clark (Robinson College, Cambridge) 2010-2011 President Oliver Claydon (Gonville and Caius College, Cambridge) Vice President Sally Ko (Imperial College London) 2011-2012 President Glen-Oliver Gowers (University College, Oxford) Vice President Ross-William Hendron (St Peter’s College, Oxford) 2012-2013 President Rachel Wright (St Peter’s College, Oxford) Vice President David Gardner (University of Nottingham) 2013-2014 President Holly Hendron (St Peter’s College, Oxford) Vice President Anne-Marie Baston (Magdalen College, Oxford) 2014-2015 President Ollie Hull (Merton College, Oxford) Vice President Cesci Adams (University of Bristol) Past and Present Moncreiff-Jones Society Endorsers Dr Jan Schnupp, Lecturer in Department of Physiology, Anatomy and Genetics at the University of Oxford Dr Bruce Griffin, professor at Surrey University, specialising in lipid metabolism, nutritional biochemistry and cardiovascular disease Dr Simon Singh, popular author and science writer, including the book 'Trick or Treatment?'

Dr Mark Wormald, Tutor of Biochemistry at the University of Oxford Dr Nick Lane , Reader in Evolutionary Biochemistry in the Department of Genetics, Evolution and Environment at UCL and popular author, including the book ‘The Vital Question’ 55

PAST MONCRIEFF TOPICS

RABIES

GENE REGULATION

LAMB SHIFT

APOPTOSIS

GM MOSQUITOES

THE UNCERTAINTY PRINCIPLE

HIV

SAVANT SYNDROME TIME DILATION THE HUMAN PAPILLOMAVIRUS DARK ENERGY ENZYME INHIBITION THE BIOCHEMISTRY OF TASTE

THE ORIGIN OF LIFE SKIN GRAFTING AROMATIC CHEMISTRY WHAT HAPPENED TO BRUCE BANNER? SNAKE VENOM REGENERATION DEALING WITH DISEASE DISPERSION THE FOUR FUNDAMENTAL FORCES THE MITOCHONDRIAL GENOME

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CARBON CAPTURE AND STORAGE

HOW ON EARTH DO YOU GET TO THE MOON?

COLLAGEN PLANT REPRODUCTION IS THE WAR ON CANCER UNWINNABLE? DEFENCE AGAINST DISEASE IN PLANTS GM CROPS

CROHN’S DISEASE HYPOTHYROIDISM AND HYPERTHYROIDISM GIRLS KNOW BEST- EVOLUTION BY SEXUAL SELECTION THE CHEMICAL CLOCK OPTICAL ISOMERISM ORIGIN OF THE HEARTBEAT STEM CELLS TYPE 1 DIABETES KETOSIS TOPSPIN: AERODYNAMICS FROM LUPIS TO FAMILIARIS

ANGELMAN SYNDROME

HOW WE MAKE SENSE OF SOUND

BUILDING BLOCKS: THE AMIDE GROUP

NEUROSCIENCE

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Society Summary

by Dan Quinton

T

he Moncrieff-Jones Society is very dear to my heart. Thanks to science we live in an extraordinary technological age. A world of Twitter and sound bites.

A world where ill-informed people will give their opinion without really understanding the facts. Science often requires a knowledge of a vast array of facts before you can begin to understand and certainly before you can give a worthwhile opinion. It requires incredible discipline yet is also, at the cutting edge, incredibly creative.

The brave students giving lectures at the Society’s fortnightly meetings receive no help from staff, and are cross questioned by the audience for around 40 minutes – they must teach themselves a vast array of facts and then understand them if they are to survive a Moncrieff-Jones Lecture! MJS must be the ultimate in terms of independent learning – a skill the top universities are looking for in their undergraduates. The MJS talks have reached an extraordinarily high standard and there are always more students wanting to do MJS talks than there are weeks available in the term.

I cannot thank Tom and Emily enough for all they have done this year. They have worked tirelessly to organise and promote the society and to maintain its position as the most popular and prestigious society in the school.

John Jones founded the Moncrieff Society in 1967, as a ‘liberal science society’ – its mission to address a gap in the range of 6th form societies. Sir Alan Moncrieff was an eminent Old Caterhamian in the medical field and John Jones was a Head of Chemistry at Caterham School for many years. When I took over the Society I decided it should be renamed the Moncrieff-Jones Society in the year that John Jones retired, as a way of recognising the massive contribution John made to Science at Caterham School.

True to the liberal spirit in which MJS was formed, meetings over the years have included the reading of scenes from Brecht’s ‘Life of Galileo’, pictures depicting the beginning of life at hydrothermal vents, and even an entertainment based on scientific themes. Individuals have spoken on interests as diverse as cell biology and thermodynamics, and intellectual tours de force have ranged from the quantum world of the very small to the vast sphere of astrophysics.

We live in an age of science. There has never been a greater time to study science. With the massive problems the world faces, it is through science that we look for solutions.

It is a testimony to the input of so many generations of Caterhamians that the society survives and thrives some 49 years on.

Dan Quinton is Head of Science at Caterham School 58

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Caterham School, Harestone Valley Road, Caterham Surrey CR3 6YA Telephone: 01883 343028 Email: enquiries@caterhamschool.co.uk

caterhamschool.co.uk

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